Narcotic antagonists are assuming increasing clinical as well as theoretical importance, yet, the behavioral pharmacology of these drugs remains largely undefined. The purpose of the proposed research project is to continue and expand upon an ongoing investigation of the behavioral effects of representative narcotic antagonists and morphine in infrahuman species. To afford maximal generality to the experimental findings a series of drugs will be evaluated in a variety of procedures in two species: rat and squirrel monkey. The following variables will be examined in the rat: locomotor activity, intracranial selfstimulation, drug discrimination, disposition of biogenic amines in discrete regions of the brain. Drug effects will be assessed on continuous avoidance behavior in the squirrel monkey with schedule parameters similar to those employed in recently completed experiments in the rat. Dose-response and time-effect concepts will be observed. The specificity of drug effects will be evaluated on the basis of: a) interactions with naloxone; b) development of tolerance and cross- tolerance. The proposed experiments will help to characterize the behavioral effects of narcotic antagonists, and will help to develop animal models for the identification and evaluation of those effects. These experiments may also elucidate some of the neuronal and neurochemical substrates that mediate the behavioral effects of narcotic antagonists and agonists. Finally, although narcotic and narcotic- antagonist analgesics have many similar agonistic actions in man, many members of the latter group have a low abuse potential, whereas the abuse potential of narcotic analgesics is high. Major differences between drugs reside in their behavioral pharmacology. Therefore, a systematic and quantitative evaluation of the behavioral effects of representative narcotic antagonists and morphine may reveal properties of the drugs that can be related to these differences in abuse potential.